Influence of effectors of prostaglandin metabolism on the toxicity induced by 7-hydroxymethyl-12-methylbenz(a)anthracene in cultured rat adrenal cells

1. 7,12-Dimethylbenz(a)anthracene (DMBA) and 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA), but not benzo(a)pyrene (BP), selectively produce necrosis in the two inner zones of the rat adrenal cortex and are toxic to cultured rat adrenocortical cells.

2. The toxicity induced by 7-OHM-12-MBA in the adrenocortical cells was partially prevented by the inhibitor of the cyclooxygenase activity of prostaglandin H synthetase, indomethacin. In contrast, indomethacin did not influence the effect of BP and DMBA on these cells.

3. Two other effectors of the prostaglandin metabolism, 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA), as well as the anti-inflammatory steroids cortisol and dexamethasone, partially protected against, whereas arachidonic acid and bradykinin exacerbated, the cytotoxicity induced by 7-OHM-12-MBA.

4. These results indicate that prostaglandin metabolism may be involved in the necrotic mechanism of 7-OHM-12-MBA in rat adrenal cortex.